The overall objective is to study regulators of alveolar surface active material (SAM) (pulmonary surfactant). In the first project, we will examine whether isoxsuprine HCl, injected into fetal rabbits, can increase release of SAM into the alveolar space. Our two indices of alveolar SAM are pressure volume relationships of the lung and surface tension measurements of lung fluid. A retrospective chart review will be carried out to find whether isoxsuprine exposure of the human fetus diminishes the risk of Respiratory Distress Syndrome (RDS). We will next study in adult cats whether the rate of utilization of SAM is diminished in the presence of constant distending airway pressure. Increasing release or decreasing utilization of SAM are of obvious relevance to the therapy of SAM deficient states, such as hyaline membrane disease. The third project will examine mechanisms that may explain the clinical observation that long rupture of maternal membranes is associated with diminished risk of RDS. Much evidence suggests that RDS is the result of long immaturity. Therefore, the amniotic cavity of pregnant sheep will be kept free of fluid for 48 hours with subsequent premature delivery of the fetus. Indices of lung maturation, e.g., electron and light microscopy, surface tension measurements of lung fluid, pressure volume relationships as well as intra-uterine pressures, serum catecholamines and steroid levels and adrenal histology will be studied and compared with results from control animals. Similar studies on newborn sheep with altered cranial pressure will be carried out, if changes of intra-uterine pressure appear to be a stimulus for lung maturation. The studies in projects two and three are aimed at finding a benign and effective means of prevention for respiratory distress syndrome. BIBLIOGRAPHIC REFERENCES: Taeusch, H.W., Jr.: New directions in the Management of RDS. Hospital Practice, 53-61, March 1975. Wyszogrodski, I., Kyei-Aboagye, K., Taeusch, H.W., Jr., and Avery, M.E.: Surfactant inactivation by hyperventilation: conservation by end-expiratory pressure. J. of Appl. Physiol. 38:461-66, March 1975.